Dendrimers are synthetic nanomolecules with well-defined chemical structures. Different strategies have been used for radiolabeling dendrimers with different radioisotopes. In this study, the aim was to conjugate dendrimers with ¹⁷⁷Lu, to observe the in vivo behavior of the labeled compound and to measure the elementary changes in tumor tissue that could be caused by ionizing radiation. PAMAM G4 dendrimers conjugated with DOTA were labeled with ¹⁷⁷Lu. The radiolabeled compound was characterized and its stability was evaluated by reverse phase high performance liquid chromatography. Radiolabeling yield was >98% and stable for 24 hours. Biodistribution studies of ¹⁷⁷Lu-DOTA-dendrimers in C57BL/6 melanoma-bearing mice showed blood clearance with hepatic and renal depuration and tumor uptake. The concentrations of Br, Ca, Cl, Fe, K, Mg, Na, Rb, S, and Zn were determined in tumor tissues of C57BL/6 mice treated with ¹⁷⁷Lu-DOTA-dendrimers and in untreated mice. The results showed decreased concentrations of Br (62%), Ca (24%), Cl (51%), K (12%) and Na (60%) and increased concentrations of Fe (8%), Mg (28%), Rb (100%), S (6%) and Zn (4%) in tumor tissues of mice treated with ¹⁷⁷Lu-DOTA-dendrimers. These data may be useful to evaluate changes in tumor tissues as indicators of damage that could be caused by ionizing radiation.

The archaeolipids (lipids extracted from archaebacterias) are non saponificable molecules that form self sealed mono or bilayers (archaeosomes-ARC). Different to liposomes with bilayers made of conventional glycerophospholipids, the bilayer of ARC posses a higher structural resistance to physico chemical and enzymatic degradation and surface hydrophobicity. In this work we have compared the binding capacity of ARC exclusively made of archaeols containing a minor fraction of sulphoglycophospholipids, with that of liposomes in gel phase on M-like cells in vitro. The biodistribution of the radiopharmaceutical 99mTc-DTPA loaded in ARC vs that of liposomes upon oral administration to Wistar rats was also determined. The fluorescence of M-like cells upon 1 and 2h incubation with ARC loaded with the hydrophobic dye Rhodamine-PE (Rh-PE) and the hydrophilic dye pyranine (HPTS) dissolved in the aqueous space, was 4 folds higher than upon incubation with equally labeled liposomes. Besides, 15% of Rh-PE and 13 % of HPTS from ARC and not from liposomes, were found in the bottom wells, a place that is equivalent to the basolateral pocket from M cells. This fact suggested the occurrence of transcytosis of ARC. Finally, 4 h upon oral administration, ARC were responsible for the 22.3 % (3.5 folds higher than liposomes) shuttling of 99mTc-DTPA to the blood circulation. This important amount of radioactive marker in blood could be a consequence of an extensive uptake of ARC by M cells in vivo, probably favored by their surface hydrophobicity. Taken together, these results suggested that ARC, proven their adjuvant capacity when administered by parenteral route and high biocompatibility, could be a suitable new type of nanoparticulate material that could be used as adjuvants by the oral route.

Dendrimers are branched nanomolecules, with a three dimensional structure, very low polydispersity and high functionality. Poly(amidoamine) (PAMAM) dendrimers are the most investigated class of dendrimers. In this study, PAMAM G4 dendrimer conjugated with HYNIC (hydrazinonicotinamide), an efficient bifunctional chelator, was characterized. Structure of the derivatized dendrimer was confirmed by ¹H-NMR and ¹³C-NMR spectra and MALDI-TOF mass spectrometry. HYNIC-dendrimer was labeled with technetium-99m testing three different co-ligands (tricine, nicotinic acid and ethylenediaminodiacetic acid). The radiolabeled complexes were characterized by reverse phase HPLC, as well as their stabilities. Radiolabeling yield was about 99% with all co-ligands and complexes were found stable for 24 h. Biodistribution studies were performed administrating tricine-^99mTc-HYNIC-dendrimer, nicotinic acid-^99mTc-HYNICdendrimer and EDDA-^99mTc-HYNIC-dendrimer to normal mice; results showed blood clearance with hepatic and renal depuration in all cases. In this sense, labeling of PAMAM G4 dendrimer with technetium-99m using HYNIC could be obtained in high yield in a simple method and with high specific activity.

Introduction: Multiple Myeloma (MM) is a haematological malignancy in which Interleukin-6 (IL-6) plays a crucial role in its growth and spread. The monoclonal antibody Tocilizumab binds strongly to IL-6 receptors, inhibiting their function. Our aim is to evaluate the potential of [177Lu]Lu-labeled Toclilzumab as a theranostic agent for MM. Methods: Tocilizumab was derivatised with DOTA-NHS ester and radiolabeled with [177Lu]Lu. The stability of the radiochemical compound was evaluated, and in vitro binding and immunoreactive fraction assays were performed. Biodistribution was assessed at 24 and 48 h post-injection (n = 5) in normal and MM-bearing BALB/c nude mice. Results: [177Lu]Lu-DOTA-Tocilizumab remained stable in all tested solutions. Epitope recognition was confirmed by cell-binding studies, and an immunoreactive fraction of 83.7% was observed. In vivo biodistribution studies revealed high tumor uptake over time, with tumor-to-muscle ratios of 11.66 ± 3.81 and 9.54 ± 1.75 at 24 and 48 h, respectively. Discussion: This study focused on the synthesis and characterisation of a new radiolabeled theranostic agent against IL6R, [177Lu]Lu-DOTA-Tocilizumab. This agent demonstrated high radiochemical stability and strong binding to IL-6R in the MM cell line. Biodistribution studies indicated selective retention of the agent in tumor tissue, highlighting its potential for targeted imaging and therapy in IL-6R-positive cancers and paving the way for future research into its application in related diseases. Conclusions: [177Lu]Lu-DOTA-Tocilizumab represents a potential theranostic agent for MM. Therefore, we expect this agent to open the way to new diagnostic and therapeutic strategies for this devastating disease.